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R W Bailey

Publications and source records attributed to R W Bailey.

At least 19 recordsLinked to original sources

Clusterin, a binding protein with a molten globule-like region.

Clusterin is a heterodimeric glycoprotein found in many tissues of the body and is the most abundant protein secreted by cultured rat Sertoli cells. The function of clusterin is unknown, but it has been associated with cellular injury, lipid transport, apoptosis, and it may be involved in the clearance of cellular debris caused by cell injury or death. Consistent with this last idea, clusterin has been shown to bind to a variety of molecules with high affinity including lipids, peptides, and proteins and the hydrophobic probe 1-anilino-8-naphthalenesulfonate (ANS). Given this variety of ligands, clusterin must have specific structural features that provide the protein with its promiscuous binding activity. Using sequence analyses, we show that clusterin likely contains three long regions of natively disordered or molten globule-like structures containing putative amphipathic alpha-helices. These disordered regions were highly sensitive to trypsin digestion, indicating a flexible nature. The effects of denaturation on the fluorescence of the clusterin-ANS complex were compared between proteins with structured binding pockets and molten globular forms of proteins. Clusterin bound ANS in a manner that was very similar to that of molten globular proteins. Furthermore, we found that, when bound to ANS, at least one cleavage site within the protease-sensitive disordered regions of clusterin was protected from trypsin digestion. In addition, we show that clusterin can function as a biological detergent that can solubilize bacteriorhodopsin. We propose that natively disordered regions with amphipathic helices form a dynamic, molten globule-like binding site and provide clusterin the ability to bind to a variety of molecules.

Amino Acid Sequence↗

Intrinsically disordered protein.

Proteins can exist in a trinity of structures: the ordered state, the molten globule, and the random coil. The five following examples suggest that native protein structure can correspond to any of the three states (not just the ordered state) and that protein function can arise from any of the three states and their transitions. (1) In a process that likely mimics infection, fd phage converts from the ordered into the disordered molten globular state. (2) Nucleosome hyperacetylation is crucial to DNA replication and transcription; this chemical modification greatly increases the net negative charge of the nucleosome core particle. We propose that the increased charge imbalance promotes its conversion to a much less rigid form. (3) Clusterin contains an ordered domain and also a native molten globular region. The molten globular domain likely functions as a proteinaceous detergent for cell remodeling and removal of apoptotic debris. (4) In a critical signaling event, a helix in calcineurin becomes bound and surrounded by calmodulin, thereby turning on calcineurin's serine/threonine phosphatase activity. Locating the calcineurin helix within a region of disorder is essential for enabling calmodulin to surround its target upon binding. (5) Calsequestrin regulates calcium levels in the sarcoplasmic reticulum by binding approximately 50 ions/molecule. Disordered polyanion tails at the carboxy terminus bind many of these calcium ions, perhaps without adopting a unique structure. In addition to these examples, we will discuss 16 more proteins with native disorder. These disordered regions include molecular recognition domains, protein folding inhibitors, flexible linkers, entropic springs, entropic clocks, and entropic bristles. Motivated by such examples of intrinsic disorder, we are studying the relationships between amino acid sequence and order/disorder, and from this information we are predicting intrinsic order/disorder from amino acid sequence. The sequence-structure relationships indicate that disorder is an encoded property, and the predictions strongly suggest that proteins in nature are much richer in intrinsic disorder than are those in the Protein Data Bank. Recent predictions on 29 genomes indicate that proteins from eucaryotes apparently have more intrinsic disorder than those from either bacteria or archaea, with typically > 30% of eucaryotic proteins having disordered regions of length > or = 50 consecutive residues.

Models, Molecular↗

Laparoscopic hernia repair: the learning curve.

The performance of a laparoscopic inguinal hernia repair requires unique technical and cognitive skills which, until recently, were not routinely taught to general surgeons. The initial experience of three surgeons with laparoscopic hernia repair was audited prospectively to assess the learning curve for the technique. From March 1992 to June 1994, transabdominal preperitoneal (TAP) mesh repair was attempted on 172 consecutive inguinal hernias. Three procedures were converted to traditional repairs. The three independent surgeons that performed the repairs had minimal or no prior clinical experience with the technique in the role as primary surgeon. The hernia repairs were divided into two groups. Group 1 consisted of the first 90 hernia repairs in the series, 30 repairs per surgeon. This group was compared to the subsequent 82 repairs (group 2), approximately 27 repairs per surgeon. Patients were followed up for a median of 31 months. Group 1 had more patients who were hospitalized overnight (37% versus 31%), a greater rate of conversion (2.2% versus 1.2%), a higher complication rate (11.7% versus 0%), a higher recurrence rate (12.2% versus 0%), and a longer delay in the return to full activity (11 weeks versus 8 weeks). Also, overall patient satisfaction with their hernia repair was slightly greater in group 2 (score, 9.0/10 versus 8.2/10). The lack of prior experience with the TAP technique (one surgeon) was associated with a marked increase in the number of conversions (two of three total conversions), complications (four of eight total), and hernia recurrences (8 of 11 total). This study demonstrates that a surgeon's initial experience with laparoscopic herniorrhaphy is associated with an identifiable learning curve. Significant improvements in complication and recurrence rates and overall patient satisfaction can be expected after the initial learning phase. Also, a complete lack of prior experience with laparoscopic herniorrhaphy is associated with a higher rate of conversion and significant increases in complications and hernia recurrences.

Adolescent↗

Hemodynamic pathogenesis of ischemic hepatic injury following cardiogenic shock/resuscitation.

Post-ischemic hepatic injury is observed commonly following cardiogenic or hypovolemic shock. We evaluated the putative roles of the alpha-adrenergic sympathetic nervous system and the renin-angiotensin axis in the pathogenesis of hepatic injury following cardiogenic shock. Previous studies have characterized the hepatic hemodynamic response to shock, while the relationship of these hemodynamic changes to ischemic hepatic injury has not been defined. Sustained (4 h) periods of pericardial tamponade (after mild hemorrhage) followed by 2 h of resuscitation generated a reproducible model of cardiogenic shock and consequent post-ischemic hepatic injury in anesthetized pigs. In a separate group of pigs, the alpha-adrenergic component of the sympathetic nervous system was ablated with phenoxybenzamine or, in other groups, the renin-angiotensin axis was ablated by either prior nephrectomy or, separately, by confirmed angiotensin converting enzyme inhibition with teprotide. The hepatic injury response in each case was reevaluated. Compared to sham-shocked pigs, those subjected to tamponade alone manifested selective splanchnic vasospasm and consequent biochemical and histological evidence of classic post-ischemic liver injury (centrilobular necrosis involving about a third of each hepatic lobule). These manifestations of splanchnic vasospasm and the consequent ischemic injury were not ameliorated by confirmed alpha-adrenergic blockade, but significantly attenuated by either method of prior ablation of the renin-angiotensin axis. This model of sustained cardiogenic shock and resuscitation generates the manifestations of ischemic hepatic injury associated with selective splanchnic vasospasm, findings consistent with previous, short-term, hemodynamic studies. The major mediator of this response, and the consequent hepatic injury, is the selective hypersensitivity of the mesenteric vasculature to the renin-angiotensin axis.

Alanine Transaminase↗

Prospective, multicenter study of laparoscopic ventral hernioplasty. Preliminary results.

BACKGROUND: A standard technique for laparoscopic ventral hernioplasty (peritoneal onlay using an expanded polytetrafluoroethylene [ePTFE] patch for hernias >/=4 cm2) is being used in a prospective, multicenter, long-term study. METHODS: Demographic, operative, and postoperative data were collected and analyzed. Follow-up clinical evaluations were conducted 7-10 days, 4 weeks, 6 months, 1 year, and then annually after surgery in all patients. RESULTS: In the first 2 years of the study, 144 patients were enrolled; nine were lost to follow-up. The mean operating time was 120 min. The mean follow-up was 222 days (range 5-731). Postoperative complications were five infections, three cases of prolonged ileus, one bowel obstruction, 23 seromas (15 resolved without intervention), and six hernia recurrences. Hospital discharge occurred a mean of 2.3 days after surgery and return to normal activity a mean of 15 days postoperatively. CONCLUSIONS: Laparoscopic prosthetic ventral hernioplasty avoids the large wound required in open repairs, with attendant complications and recurrences, and appears safe, especially if an ePTFE mesh is used. Compared with conventional open ventral hernioplasty, the laparoscopic technique may also allow shorter hospitalization and a quicker return to normal activities after surgery.

Adult↗

Laparoscopic management of acute cholecystitis.

The role of laparoscopic surgery in patients presenting with acute cholecystitis remains controversial. From September 1989 through August 1992, a total of 720 patients underwent cholecystectomy. Ninety-six were unplanned admissions with a clinical diagnosis of acute cholecystitis. Laparoscopic surgery was attempted in 83 patients. Thirteen individuals were not offered laparoscopy because of the surgeon's inexperience. Twenty-two (27%) patients required the laparoscopic procedure converted to an open laparotomy. The mean postoperative hospital stay for patients undergoing laparoscopic cholecystectomy was 3.3 days versus 6.8 days for the laparotomy group. There was no mortality and no bile duct or major vascular injuries in either group. The overall operative morbidity rate was 16.9%. Laparoscopic cholecystectomy appears to be a safe and beneficial option in selected patients with acute cholecystitis. A low threshold for conversion to laparotomy appeared to be an important factor in maintaining a low incidence of operative complications. Several modifications to the technique of laparoscopic cholecystectomy have evolved over the 3-year study period and are described.

Acute Disease↗

Laparoscopic cholecystectomy and common bile duct stones. The utility of planned perioperative endoscopic retrograde cholangiography and sphincterotomy: experience with 63 patients.

OBJECTIVE: Planned perioperative endoscopic retrograde cholangiography (ERC) and sphincterotomy (ES) for suspected or proven common bile duct stones (CBDS) has been attempted in 63 of 540 consecutive patients undergoing laparoscopic cholecystectomy (LC). Experience with this intervention has been studied with respect to accuracy, efficacy, and safety. SUMMARY BACKGROUND DATA: The optimal management of CBDSs in the era of LC is not defined. Methods exist for the laparoscopic manipulation of the common bile duct; however, experience is limited. Until surgeons become comfortable with this more demanding technique, ERC and ES will have a prominent role in the perioperative management of CBDSs. METHODS: A preoperative group (n = 41) included all candidates for LC with historical, biochemical, or radiologic evidence of CBDSs. A postoperative LC group (n = 22) included patients with stones diagnosed by intraoperative cholangiogram (IOC) (n = 6) or with signs or symptoms of retained, but unproven, CBDSs (n = 16). RESULTS: Thirty-six (88%) of the preoperative attempts were successful. Stones were identified in 18 cases and ES and duct clearance were achieved in all 18. In the postoperative group, ERC was successful in 21 (95%) cases. Calculi were demonstrated in 5 of 6 patients with a positive IOC and 6 of 16 with clinically suspected retained stones. ES and duct clearance were achieved in all 11 patients with documented CBDSs. Overall, ERC was accomplished in 90% of cases. Stones were identified in 51% of cases and all stones were cleared by ES. Morbidity was confined to four cases of self-limited pancreatitis (6%). There were no deaths. CONCLUSIONS: The perioperative management of CBDSs is an appealing approach for patients anticipating the benefits of LC, at least until the laparoscopic manipulation of the common bile duct becomes a more widely accepted technique.

Adult↗

Laparoscopic splenectomy in the management of immune thrombocytopenia purpura.

The role of splenectomy in the management of immune thrombocytopenia purpura is well known. Recent improvements in laparoscopic technology have significantly expanded the variety of general surgical procedures amenable to a minimally invasive approach. An initial experience of four cases of immune thrombocytopenic purpura managed by laparoscopic splenectomy is presented. The entire procedure was completed under laparoscopic guidance in three of four cases, and a counterincision was required to control bleeding in one patient. The procedure is performed with five operating ports including a camera port, two retraction ports, and two dissection ports. Dissection begins at the lower pole of the spleen and progresses cephalad to the hilum where major vessels are individually ligated and divided. The short gastric vessels are divided with a linear laparoscopic stapler. The lateral peritoneal attachments are divided, and the spleen is removed intact through a 6 cm fascial incision at the umbilicus. Laparoscopic splenectomy appears to be a safe and efficacious procedure that is useful in the management of certain hematologic diseases and may ultimately be performed for a variety of pathologic conditions involving the spleen.

Adult↗

Laparoscopic management of acute and chronic cholecystitis.

Contrary to earlier predictions, it appears that acute cholecystitis should be considered a relative rather than an absolute contraindication to laparoscopic surgery. The most important parameter in determining the feasibility of attempting laparoscopic cholecystectomy in the setting of acute inflammation appears to be the experience of the surgeon. This also appears to be true when encountering individuals with elements of long-standing chronic cholecystitis. Although laparoscopic intervention in such patients is associated with a greater likelihood of conversion to open laparotomy, the incidence of major biliary and nonbiliary complications appears to be low. In addition, these patients enjoy the same benefits of laparoscopic surgery as those undergoing elective surgery.

Acute Disease↗

Laparoscopic cholangiography. Results and indications.

One hundred sixty-five operative cholangiograms were attempted in 364 patients who underwent laparoscopic cholecystectomy (45%). Laparoscopic cholangiography was successful in 150 of 165 attempts (91%). Eighty-nine per cent of studies were normal (134/150) and 11% were abnormal (16/150). All 134 patients with normal cholangiograms remained asymptomatic (false-negative rate, 0%). False-positive studies occurred in 3 of 150 (2%) total cholangiograms and 3 of 12 (25%) abnormal cholangiograms consistent with choledocholithiasis. A total of 16 of 364 patients had proven common bile duct stones (4.4%). Eight of the sixteen stones were removed by preoperative endoscopic retrograde cholangiopancreatography/sphincterotomy. Five of sixteen stones were found at cholangiography, four of which were unsuspected (4/150, 2.6%). Retained common duct stones were found in 3 of 214 patients not undergoing cholangiography (1.4%). No complications or deaths occurred that were due to cholangiography. One biliary injury occurred (1/364, 0.3%), in a patient with aberrant anatomy who did not undergo cholangiography. Laparoscopic cholangiography is a safe technique with a success rate greater than 90%. Routine cholangiography is presently recommended for prevention of biliary injury, detection of stones in the cystic and common ducts, and for training purposes, especially during the learning phase of laparoscopic cholecystectomy.

Cholangiography↗

Laparoscopic cholecystectomy: a review of 12,397 patients.

We reviewed the cumulative experience with laparoscopic cholecystectomy reported in the surgical literature, including 12,397 patients selected to undergo laparoscopic cholecystectomy, 95% of which were performed on an elective basis. Although the indications for operation varied, 90% of patients had evidence of cholelithiasis and biliary colic. Conversion to open cholecystectomy was required in 534 patients (4%); of these, 52% were converted because of acute or chronic inflammation or adhesions. Laparoscopic cholangiography was attempted in 3,696 of 9,231 patients (40%) and was successful in 84%. The incidence of major bile duct injury, minor bile duct injury, bile leak, and overall morbidity was 0.3%, 0.1%, 0.4%, and 4%, respectively. The mortality rate was 0.08%. Results from individual reports indicate that 54% to 98% of patients were discharged on the 1st or 2nd postoperative day, and 77% to 98% returned to full activity within 7 to 14 days. The incidence of bile duct injury, overall morbidity, and mortality compare favorably with published reports for open cholecystectomy. The collective data would also indicate that laparoscopic cholecystectomy is a safe and efficacious procedure that offers a viable alternative to conventional cholecystectomy.

Cholangiography↗

Laparoscopic general surgery: current status and future prospects.

The capability of performing major abdominal surgery while avoiding a large abdominal incision has clear benefits for patient care. Laparoscopic cholecystectomy can reduce hospital stays and the length of the recovery period, as well as decrease postoperative pain, diminish scarring, and provide significant cost savings.

Cholecystectomy↗

The use of radionuclide imaging in the evaluation of suspected biliary damage during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy offers a reliable and effective alternative to the standard operative cholecystectomy with reduced morbidity and patient recovery time. We report three cases in which radionuclide hepatobiliary imaging was utilized to evaluate the integrity of the extrahepatic biliary ducts following suspected biliary damage during the procedure, documenting bile leakage in two of the patients.

Adult↗

Laparoscopic guided cholecystectomy.

Cholecystectomy remains the most effective form of therapy for patients with symptomatic cholelithiasis. An alternative method of gallbladder removal, laparoscopic guided cholecystectomy, was attempted in 100 patients. Five patients required conversion of the laparoscopic procedure to an open laparotomy for the following reasons: discovery of a pancreatic malignancy in one patient, extensive adhesions in one, presence of an aberrant accessory right hepatic duct in one, common hepatic duct injury in one, and avulsion of the cystic duct in one. Both ductal injuries occurred during the early phase of the clinical program. In those patients undergoing laparoscopic cholecystectomy, 93 were discharged within 24 hours of surgery and 94 returned to normal activity within 1 week. Laparoscopic guided cholecystectomy appears to offer a number of advantages in patient care as well as a significant reduction in health care expenses for gallbladder disease. Appropriate training in laparoscopic surgery is necessary in order to avoid operative complications.

Adolescent↗

The Baltimore experience with laparoscopic management of acute cholecystitis.

Laparoscopic cholecystectomy has rapidly emerged as a popular alternative to traditional laparotomy and cholecystectomy. Acute cholecystitis has been considered to be a relative or absolute contraindication to laparoscopic surgery. After gaining extensive experience in laparoscopic biliary tract surgery, this procedure was attempted in 15 patients with acute cholecystitis. All patients were operated on within 72 hours of admission. In five patients, the laparoscopic procedure was converted to an open laparotomy; in one patient, a localized abscess was found, and in the other four patients, extensive inflammation and edema precluded a safe dissection of the vascular and ductal structures. Laparoscopic cholangiography was performed in 14 patients and proved valuable in demonstrating the ductal anatomy. Patients were discharged an average of 2.7 days after the laparoscopic procedure. Laparoscopic cholecystectomy may be safely performed by experienced surgeons in patients with acute cholecystitis. To ensure a low complication rate, a low threshold for converting the procedure to an open laparotomy must be maintained if the ductal and vascular anatomy cannot be safely demonstrated.

Acute Disease↗

Celiomesenteric anomaly and aneurysm: clinical and etiologic features.

The development of aneurysmal disease involving the rarely encountered celiomesenteric anomaly is extremely unusual. Aneurysmal disease of the celiac or superior mesenteric arteries is itself an extremely uncommon finding, accounting for less than 10% of all visceral artery aneurysms. The existence of aneurysmal disease involving a celiomesenteric anomaly has been alluded to only briefly in two previous clinical reports. We review the case of a young woman with aneurysmal disease involving a common celiomesenteric trunk. The patient underwent excision of the aneurysm with successful vascular reconstruction. Although extremely unusual, the development of this extremely rare lesion can be predicted on the basis of specific etiologic theories. Variations in the patterns of embryologic formation of the visceral arteries account for the development of celiomesenteric anomalies, whereas atherosclerosis, medial degeneration, and infection lead to the development of most visceral aneurysms. Surgical treatment of celiac or mesenteric aneurysms is almost always indicated. Awareness of potential vascular anomalies and patterns of collateral circulation are necessary for appropriate surgical intervention.

Aneurysm↗